Herpes simplex virus alters Alzheimer's disease biomarkers - A hypothesis paper

Introduction: Human herpes simplex virus 1 (HSV1) is discussed to induce amyloid-beta (A beta) accumulation and neurofibrillary tangles of hyperphosphorylated tau (pTau) in Alzheimer's disease (AD) in cell culture and animal models. A beta appears to be virostatic. We investigated the association between intrathecal antibodies against HSV or cytomegalovirus (CMV) and cerebrospinal fluid (CSF) AD biomarkers. Methods: beta(42)/A beta(40) ratio, pTau, and tTau were measured in CSF of 117 patients with early AD positive for amyloid pathology (A+) and 30 healthy controls (A-). CSF-to-serum anti-HSV1/2-IgG antibody indices (AI-IgG(HSV1/2)) and CMV (AI-IgG(CMV)) were determined by enzyme-linked immunosorbent assay (ELISA). Results: Exclusively in HSV1-seropositive AD, pTau was positively and significantly predicted by AI-IgG(HSV1/2) and negatively by the A beta(42)/A beta(40) ratio in both univariate and multivariate regression analyses. Furthermore, a significant and negative interaction between the AI-IgG(HSV1/2) and A beta(42)/A beta(40) ratio on pTau was found.Discussion: The results support the hypothesis that HSV infection contributes to AD.